Antioxidant and Antiproliferative Activities of Eclipta prostrata (L.) L. Extract and Isolated Compounds.

The primary objective of this study was to elucidate the chemical composition, antioxidant properties, and antiproliferative activities of Eclipta prostrata extracts. Two flavonoids, 3'-O-methylorobol and apigenin 7-sulfate, were isolated from the ethyl acetate (EtOAc) extract of E. prostrata. The total phenolic and flavonoid contents of the E. prostrata extracts, as well as their overall antioxidant activities as measured using the 2,2-diphenyl-1-picrylhydrazyl and reducing power assays, were investigated. The E. prostrata EtOAc extract exhibited significantly greater antioxidant activities in both assays and higher phenol and flavonoid contents than the other extracts. The potential antiproliferative properties of the E. prostrata extracts and isolated compounds were investigated in vitro against the AGS, A549, and HT-29 cancer cell lines and the normal human HEK-293 cell line using the MTT assay. Annexin V-FITC/PI staining analysis and quantitative real-time PCR were used to assess AGS cell apoptosis. At a concentration of 100 µg/mL, the EtOAc extract of E. prostrata reduced AGS cell viability and proliferation by inducing apoptosis through the alteration of gene expression in the apoptotic cascade. These results highlight E. prostrata as a promising source of anticancer compounds.

Anti-cancer effect of pristimerin by inhibition of HIF-1α involves the SPHK-1 pathway in hypoxic prostate cancer cells.

BACKGROUND: Hypoxia is a typical character of locally advanced solid tumours. The transcription factor hypoxia-inducible factor 1α (HIF-1α) is the main regulator under the hypoxic environment. HIF-1α regulates various genes to enhance tumour progression, angiogenesis, and metastasis. Sphingosine kinase 1 (SPHK-1) is a modulator of HIF-1α. METHODS: To investigate the molecular mechanisms of pristimerin in association with SPHK-1 pathways in hypoxic PC-3 cancer cells. Vascular endothelial growth factor (VEGF) production, cell cycles, and SPHK-1 activity were measured, and western blotting, an MTT assay, and an RNA interference assay were performed. RESULTS: Pristimerin inhibited HIF-1α accumulation in a concentration- and-time-dependent manner in hypoxic PC-3 cells. Pristimerin suppressed the expression of HIF-1α by inhibiting SPHK-1. Moreover, inhibiting SPHK-1 with a sphingosine kinase inhibitor enhanced the suppression of HIF-1α, phosphorylation AKT, and glycogen synthase kinase-3ß (GSK-3ß) by pristimerin under hypoxia. Furthermore, a reactive oxygen species (ROS) scavenger enhanced the inhibition of HIF-1α and SPHK-1 by pristimerin. CONCLUSION: Taken together, these findings suggest that pristimerin can exert an anti-cancer activity by inhibiting HIF-1α through the SPHK-1 pathway.

New Preclinical Development of a c-Met Inhibitor and Its Combined Anti-Tumor Effect in c-Met-Amplified NSCLC.

c-Met is a receptor tyrosine kinase with no commercially available product despite being a pivotal target in cancer progression. Unlike other c-Met inhibitors that fail clinically, ABN401 is a newly synthesized c-Met inhibitor that is not potentially degraded by aldehyde oxidase (AO) in human liver cytosol. This study aimed to determine the physicochemical stability, pharmacokinetics in beagle dogs, and therapeutic effect of ABN401 in a c-Met-amplified non-small-cell lung cancer (NSCLC) patient-derived xenograft (PDX) model. ABN401 was found to be a weak basic compound, with pKa and log P values of 7.49 and 2.46, respectively. It is poorly water-soluble but soluble at acidic pH. The accelerated storage stability is dependent on temperature, but the purity remains at over 97% after 6 months. The bioavailability is approximately 30% in dogs and it is highly efficient in the PDX model, achieving around 90% tumor growth inhibition in combination with erlotinib. These observations indicate that the compound is acceptable for the next phase of trials.

Signet ring cell carcinoma of early gastric cancer, is endoscopic treatment really risky?

Signet ring cell carcinoma (SRC) is a poorly differentiated cancer of the stomach. Generally, poorly differentiated cancer is believed to show poor prognosis and aggressive behavior. Recently, however, there is debate on the aggressiveness of SRC in early gastric cancer (EGC). We therefore studied postoperation biopsies to investigate the aggressiveness of SRC in EGC.We reviewed medical records of patients with EGC who had surgery from January 2011 to December 2015 in a tertiary hospital in Daejeon, South Korea. We evaluated the histologic type, invasion depth, lymphovascular invasion (LVI), and lymph node (LN) metastasis.A total of 822 EGC lesions from 789 patients were studied. Approximately 498 differentiated cancer, 65 poorly differentiated cancer, 91 SRC, 26 poorly differentiated with SRC, 41 mixed type, 10 medullary carcinoma, and 91 poorly cohesive carcinoma other than SRC were included. LN metastasis was associated with the histologic type of EGC (P = .000). Nine percent of differentiated cancer, 21.5% of poorly differentiated cancer, 5.5% of SRC, 11.5% of poor differentiation with SRC, 26.8% of mixed type, 20% of medullary type, and 15.4% of poorly cohesive carcinoma other than SRC showed LN metastasis. The risk of SRC was not higher than well to moderated differentiated cancer (odds ratio [OR] = 0.842, P = .768). Risk of LVI was also similar with LN metastasis. Compared with differentiated cancer, OR of SRC was 1.969 (P = .172).Our results show that SRC is not more aggressive than differentiated cancer. SRC may be considered a candidate for endoscopic treatment.

Genes co-amplified with ERBB2 or MET as novel potential cancer-promoting genes in gastric cancer.

Gastric cancer (GC), one of the most common cancers worldwide, has a high mortality rate due to limited treatment options. Identifying novel and promising molecular targets is a major challenge that must be overcome if treatment of advanced GC is to be successful. Here, we used comparative genomic hybridization and gene expression microarrays to examine genome-wide DNA copy number alterations (CNAs) and global gene expression in 38 GC samples from old and young patients. We identified frequent CNAs, which included copy number gains on chromosomes 3q, 7p, 8q, 20p, and 20q and copy number losses on chromosomes 19p and 21p. The most frequently gained region was 7p21.1 (55%), whereas the most frequently deleted region was 21p11.1 (50%). Recurrent highly amplified regions 17q12 and 7q31.1-7q31.31 harbored two well-known oncogenes: ERBB2 and MET. Correlation analysis of CNAs and gene expression levels identified CAPZA2 (co-amplified with MET) and genes GRB7, MIEN1, PGAP3, and STARD3 (co-amplified with ERBB2) as potential candidate cancer-promoting genes (CPGs). Public dataset analysis confirmed co-amplification of these genes with MET or ERBB2 in GC tissue samples, and revealed that high expression (except for PGAP3) was significantly associated with shorter overall survival. Knockdown of these genes using small interfering RNA led to significant suppression of GC cell proliferation and migration. Reduced GC cell proliferation mediated by CAPZA2 knockdown was attributable to attenuated cell cycle progression and increased apoptosis. This study identified novel candidate CPGs co-amplified with MET or ERBB2, and suggests that they play a functional role in GC.

Fermented Rhus verniciflua Stokes Extract Exerts an Antihepatic Lipogenic Effect in Oleic-Acid-Induced HepG2 Cells via Upregulation of AMP-Activated Protein Kinase.

Rhus verniciflua Stokes has been used as a traditional medicine and food supplement in Korea. In the present study, fermented R. verniciflua Stokes extract (FRVE), an allergen-free extract of R. verniciflua Stokes fermented with the yeast Saccharomyces carlsbergensis, was assessed for its lipid-lowering potential in an in vitro non-alcoholic fatty liver disease model. FRVE markedly suppressed lipid accumulation and intracellular triglycerides (TGs) in the presence of oleic acid (OA). Additionally, FRVE decreased both mRNA and protein levels of lipid-synthesis- and cholesterol-metabolism-related factors, such as sterol regulatory element-binding protein-1 (SREBP-1), fatty acid synthase (FAS), glycerol-3-phosphate acyltransferase (GPAT), and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), in OA-induced HepG2 cells. Moreover, FRVE activated low-density lipoprotein receptor (LDLR), AMP-activated protein kinase (AMPK), and fatty acid oxidation-related factors peroxisome proliferator activated receptor α (PPARα) and carnitine palmitoyltransferase 1 (CPT-1). Further, the AMPK inhibitor compound C suppressed the increased expression of AMPK phosphorylation induced by FRVE. Phenolics and cosanols in FRVE increased the phosphorylation of AMPK and decreased that of SREBP-1. Taken together, our findings suggest that FRVE has antilipogenic potential in non-alcoholic fatty livers via AMPK upregulation.

Long-Term Survival after T-cell Lymphoblastic Lymphoma Treated with One Cycle of Hyper-CVAD Regimen.

T-lymphoblastic lymphoma (T-LBL) is a rare form of aggressive non-Hodgkin's lymphoma. The standard approach for management of T-LBL involves intensive multiagent chemotherapy regimens for induction and consolidation phases with central nervous system prophylaxis and a maintenance phase lasting 12-18 months. We report on a case of long-term survival after one cycle of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) and high-dose methotrexate. A 30-year-old woman diagnosed with T-LBL with a large mediastinal mass underwent one cycle of hyper-CVAD. Four days after the start of treatment, the mediastinal mass was markedly reduced. Treatment continued with one cycle of consolidation chemotherapy, comprising high-dose methotrexate and high-dose cytarabine. The patient then refused all further chemotherapeutic treatment. Seven years have passed without relapse.

A case on streptococcal pneumonia associated with leptomeningitis, osteomyelitis and epidural abscess in a patient with AIDS.

Patients with acquired immunodeficiency syndrome (AIDS) are at higher risks of bacterial pneumonia than the general population, and the pathogen is the most commonly involved Streptococcus pneumoniae. We hereby report a case of pneumococcal pneumonia associated with leptomeningitis, osteomyelitis and epidural abscess in a patient with AIDS. He is being successfully treated with ampicillin/sulbactam and clindamycin. And because the pneumococcal infection is usually associated with morbidity and mortality rates in the setting of AIDS, we should consider for pneumococcal vaccinations among the AIDS populations.

Mycotic abdominal aortic aneurysm caused by bacteroides thetaiotaomicron and acinetobacter lwoffii: the first case in Korea.

Mycotic aneurysms are uncommon, but are fatal without appropriate management. Previous reports have shown that anaerobes and gram-negative organisms are less common but more dangerous than other causative agents of mycotic aneurysm. We report the case of a 60-year-old man with poorly controlled diabetes mellitus and atherosclerosis in the aorta, and a 10-day of history of lower abdominal pain and fever. This man was diagnosed with an uncommon abdominal aorta mycotic aneurysm caused by Bacteroides thetaiotaomicron and Acinetobacter lwoffii. The aneurysm was successfully treated with antibiotics therapy and aorto-bi-external iliac artery bypass with debridement of the infected aortic wall. We present this case together with a review of the relevant literature.

Percutaneous closure of an iatrogenic ventricular septal defect following concomitant septal myectomy at the time of aortic valve replacement.

A 77-year-old female patient underwent aortic valve replacement (AVR) with concomitant septal myectomy and tricuspid annuloplasty. Her symptoms did not improve after a successful operation. Echocardiogram demonstrated the presence of an iatrogenic ventricular septal defect (VSD). It was muscular in location and not the usual AVR with membraneous type of VSD, suggesting a complication from the myectomy. Percutaneous closure of the VSD remained the only feasible option due to her poor overall medical status. A 14-mm Amplazter VSD occluder was deployed successfully, by means of the trans-septal technique. She has improved very well postoperatively.